The Cori cycle, named after its discoverers, Carl Ferdinand Cori and Gerty Cori, refers to the metabolic pathway in which lactate produced by anaerobic glycolysis in the muscles moves to the liver and is converted to glucose, which returns to the muscles and is cyclically metabolized back to lactate. Muscular activity requires ATP, provided by the breakdown of glycogen in the skeletal muscles; the breakdown of glycogen, a process known as glycogenolysis, releases glucose in the form of glucose 1-phosphate. The G1P is converted to G6P by the enzyme phosphoglucomutase. G6P is fed into glycolysis, a process that provides ATP to the muscle cells as an energy source. During muscular activity, the store of ATP needs to be replenished; when the supply of oxygen is sufficient, this energy comes from feeding pyruvate, one product of glycolysis, into the citric acid cycle. When oxygen supply is insufficient during intense muscular activity, energy must be released through anaerobic metabolism. Lactic acid fermentation converts pyruvate to lactate by lactate dehydrogenase.
Most fermentation regenerates NAD+, maintaining the NAD+ concentration so that additional glycolysis reactions can occur. The fermentation step oxidizes the NADH produced by glycolysis back to NAD+, transferring two electrons from NADH to reduce pyruvate into lactate. Instead of accumulating inside the muscle cells, lactate produced by anaerobic fermentation is taken up by the liver; this initiates the other half of the Cori cycle. In the liver, gluconeogenesis occurs. From an intuitive perspective, gluconeogenesis reverses both glycolysis and fermentation by converting lactate first into pyruvate, back to glucose; the glucose is supplied to the muscles through the bloodstream. If muscle activity has stopped, the glucose is used to replenish the supplies of glycogen through glycogenesis. Overall, the glycolysis steps of the cycle produce 2 ATP molecules at a cost of 6 ATP molecules consumed in the gluconeogenesis steps; each iteration of the cycle must be maintained by a net consumption of 4 ATP molecules.
As a result, the cycle cannot be sustained indefinitely. The intensive consumption of ATP molecules in the Cori cycle shifts the metabolic burden from the muscles to the liver; the cycle's importance is based on the prevention of lactic acidosis in the muscle under anaerobic conditions. However before this happens the lactic acid is moved out of the muscles and into the liver; the cycle is important in producing ATP, an energy source, during muscle activity. The Cori cycle functions more efficiently; this allows the oxygen debt to be repaid such that the citric acid cycle and electron transport chain can produce energy at peak efficiency. The Cori cycle is a much more important source of substrate for gluconeogenesis than food; the contribution of Cori cycle lactate to overall glucose production increases with fasting duration before plateauing. After 12, 20, 40 hours of fasting by human volunteers, gluconeogenesis accounts for 41%, 71%, 92% of glucose production, but the contribution of Cori cycle lactate to gluconeogenesis is 18%, 35%, 36%, respectively.
The remaining glucose production comes from protein breakdown, muscle glycogen, glycerol from lipolysis. The drug metformin can cause lactic acidosis in patients with kidney failure because metformin inhibits the hepatic gluconeogenesis of the Cori cycle the mitochondrial respiratory chain complex 1; the buildup of lactate and its substrates for lactate production and alanine, lead to excess lactate. The excess lactate would be cleared by the kidneys, but in patients with kidney failure, the kidneys cannot handle the excess lactic acid. Alanine cycle Citric acid cycle Smith, A. D. Datta, S. P. Smith, G. Howard, Campbell, P. N. Bentley, R. et al. Oxford Dictionary of Biochemistry and Molecular Biology. New York: Oxford University Press
Witold "Vic" Walczak is the legal director of the American Civil Liberties Union of Pennsylvania. Walczak was born in Sweden on January 17, 1961 to Polish parents, his grandfather survived the Treblinka extermination camp. After the war his family was exiled from Poland by the incoming Communist Government, he emigrated to the United States at age three, spent much of his childhood in Scotch Plains, New Jersey. Walczak attended Colgate University, where he played Division I majored in Philosophy. While at Colgate, he helped the Polish trade union Solidarity to resettle refugees in the United States, he graduated in 1983, traveled that summer to Poland, under martial law. While assisting Solidarity in covert operations, Walczak was subjected to police brutality, a strip search, says that he narrowly avoided being imprisoned in Krakow. Walczak attended Boston College Law School, graduating cum laude in 1986. Starting in 1986, he worked with the Prisoner Assistance Project of the Legal Aid Bureau in Baltimore, Maryland.
In 1991, Walczak's wife, a doctor, was offered a job in Pittsburgh. After first applying to become a prosecutor with the U. S. Attorney's office, he was hired as the executive director of the Pittsburgh Chapter of the ACLU's Pennsylvania affiliate. In 2004, Walczak was named legal director for the statewide affiliate. Walczak oversaw the ACLU of Pennsylvania's 2005 challenge to the Dover Area School District's policy requiring the teaching of Intelligent Design; this case, the first federal challenge to such requirements in public schools, has been credited with ending legal efforts by the Intelligent Design movement to introduce creationism into public school curriculum. The ACLU prevailed in the District Court, after all eight school board members who voted for the Intelligent Design requirement were defeated by opponents who opposed the teaching of Intelligent Design in a science classroom, the school board did not appeal. Beginning in 2006, Walczak oversaw the ACLU of Pennsylvania's challenge to the Illegal Immigration Relief Act ordinances in Hazleton, arguing the case before the United States District Court and the United States Court of Appeals for the Third Circuit.
The case was notable as the first federal trial challenging local efforts to regulate immigration. The ACLU won both in the District Court and on appeal, but the Supreme Court vacated the Third Circuit decision in June 2011, in light of its ruling in Chamber of Commerce v. Whiting, which addressed a similar law in Arizona; the parties await a new ruling from the Third Circuit. Walczak is a fan of Bruce Springsteen's music, has cited Springsteen's song "Part Man, Part Monkey" as a source of inspiration during the Dover trial. Http://www.padnet.org/archWalczak.html http://thinkexist.com/quotes/witold_walczak/ http://blog.constitutioncenter.org/featured-guest-blogger-witold-j-walczak-2/
The Pennsylvania Governor's School for the Arts was one of the Pennsylvania Governor's Schools of Excellence, a group of five-week summer academies for gifted high school students in the Commonwealth of Pennsylvania. The school was hosted each summer by Mercyhurst College. PGSA was defunded by Pennsylvania's 2009–2010 state budget. Pennsylvania Governor's School for the Arts was established earliest among eight such Governor's schools. Like other Pennsylvania Governor's Schools of Excellence, PGSA operated on a state-funded, scholarship basis. Upon its inception in 1973, PGSA was hosted at Bucknell University in Lewisburg under the direction of Arthur Gatty, who led the program until 1988. In 1990, the program was relocated to Mercyhurst College in Erie; the most recent program director was Douglas Woods, an English teacher in the Butler Area school district. Only residents of the Commonwealth of Pennsylvania were permitted to participate in the program. Additionally, only applicants rising to 11th or 12th grades of high school were considered.
Students were required to live in dormitories for the full five weeks of the program. Admission into the program was competitive—annually 2000 students competed through a rigorous three-step process, for 200 spots in the program. Similar to a college experience, students took various classes associated with a "major" in one of five art areas: creative writing, music, theater, or visual arts. In addition to these classes, students selected an elective class in an art area other than their primary. Collaboration and multifaceted projects were common. Alongside classes, nightly performances and gallery shows combined with a broad range of social activities and special events to create a unique experience similar to that of an artists' colony. Mr. Woods emphasized that the goals of PGSA were to create an environment where gifted students could learn and grow as artists, audience members, advocates for the Arts, he adopted Seize the Day, as a motto for the summer program. Fiction taught by Dave Griffith Poetry taught by Brandon Som Ballet Jazz Modern Composition Instrumental Performance Woodwinds Piano Strings Percussion Brass Guitar Vocal Performance Performance Theater Technical Theater Architectural Design Ceramics Graphic Design Taught by Dennis Childers Painting Photography Taught by Terry Wild, Mike Chagnon Sculpture Creative Writing Dance Film Criticism Music Musical Theater Theater Visual Arts Yoga Governor Ed Rendell's 2009–2010 budget proposed cutting funding for all the schools in the PGSE program, including PGSA.
The program was discontinued after 36 years of operation. Kevin Bacon Melinda Wagner Richard O'Donnell Camillia Sanes Aaron Jay Kernis Megan Gallagher Gary Schocker Boris Bally Ian Gallanar Daniel Roebuck Alice Sebold Julia Kasdorf Tina Fey Ari Hoenig Asali Solomon Steven Burns Meagan Miller Matthew Hoch Zachary Quinto Neal Dodson Jessica Dickey Stephen Karam Katharine Beutner Gillian Jacobs Andy Mientus Barry Bova Maggie Carr Archive of PGSA page at Drexel University The Pennsylvania Governor's Schools of Excellence Savepgse's YouTube Channel National Conference of Governor's Schools Pennsylvania Arts Education Network - Pennsylvania Governor's School for the Arts Alumni Network